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Lysergic acid diethylamide, or LSD, is a potent psychoactive substance that is commonly classified as a hallucinogen or psychedelic drug. The effects of LSD vary substantially depending on the dose, the mood of the individual taking the drug, and the environment the drug is taken in. Some common effects include mental and physical stimulation, perceptual distortions, and generally positive mood states.
Although we have some understanding of LSD’s activity in the brain, it is not fully understood how this activity leads to the subjective experiences people have while taking the drug. Regardless, it is thought that LSD’s activity at a subtype of serotonin receptor known as the 5-HT2A receptor is critical to the drug’s psychedelic effects. LSD acts as a partial agonist at the 5-HT2A receptor, which means that it binds to the 5-HT2A receptor and generates a response that is a fraction of what the natural ligand, serotonin, generates. LSD also interacts with other receptors, although the role of these receptors in the effects of LSD is less clear. For example, LSD binds to other serotonin receptor subtypes as well as some subtypes of dopamine and adrenergic receptors. Research suggests that one large-scale effect of LSD on the brain is increased glutamate transmission in the frontal cortex, which is thought to play a role in the effects of LSD.
Repeated administration of LSD over several days promotes rapid tolerance, where the drug has much less of an effect than it did initially. This tolerance is thought to be associated with the down-regulation, or decrease in number, of 5-HT2A serotonin receptors. LSD is not, however, considered to be addictive. And, although it is a potent drug, it is generally considered to be non-toxic and safe in terms of its effects on the body. [1][2][3]